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Effects of quinagolide (CV 205-502), a selective D2-agonist, on vascular reactivity in patients with a
C W Bodmer1, S L Atkin, M W Savage
1Department of Endocrinology, Royal Liverpool University Hospital, UK.
Background:
Quinagolide (CV 205 502) is a dopamine D2-receptor agonist which has proved effective in the treatment of prolactinomas, reducing both serum PRL and tumour size. Some of its D2-receptor effects are mediated via alpha-adrenoceptors, which have a major influence on the control of vascular tone. The aim of this study was to examine the influence of quinagolide on in-vivo dorsal hand vein vascular responses to noradrenaline in patients with a prolactinoma.
Design And Patients:
Seven female patients with prolactinomas (age 37 (28-46) years), intolerant of bromocriptine, were studied before and after 3 months treatment with quinagolide (0.75-1.5 mg/day). Patients were otherwise disease free, were taking no other medication, and had been on no other medication (including bromocriptine) for at least 3 months prior to enrollment into the study.
Measurements:
Vascular responses to locally infused noradrenaline were measured in dorsal hand veins using an established technique. PRL, oestradiol, FSH, LH, blood pressure and body mass index were also measured before and after 3 months treatment.
Results:
Quinagolide significantly reduced PRL in all 7 patients (1795 (696-4680) (mean (range)) vs 488 (290-868) mU/l, P = 0.001), with no effect on the other parameters, including mean arterial pressure (88 (2) vs 87 (4) mmHg, P = 0.6). Vascular reactivity to noradrenaline was significantly increased after 3 months therapy: log10 dose estimated to cause 50% vasoconstriction (ED50) 1.37 (0.12) vs 0.85 (0.12) ng/min (P = 0.003; a lower ED50 indicates less noradrenaline is required to constrict the vein by 50%).
Conclusions:
Vasoconstrictor responses to noradrenaline were increased in all patients after 3 months treatment with quinagolide. Peripheral veins carry alpha-adrenoceptors analogous to those of systemic resistance vessels. If this increased vasoconstrictor response in patients with prolactinomas was occurring in hypophyseal vessels, it would lead to reduced tumour blood supply. Quinagolide may therefore reduce tumour blood flow, which may be one factor responsible for its effectiveness in these patients.